Sodium Channel SCN3A (Na(V)1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development

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Smith , R S , Kenny , C J , Ganesh , V , Jang , A , Borges-Monroy , R , Partlow , J N , Hill , R S , Shin , T , Chen , A Y , Doan , R N , Anttonen , A-K , Ignatius , J , Medne , L , Bönnemann , C G , Hecht , J L , Salonen , O , Barkovich , A J , Poduri , A , Wilke , M , de Wit , M C Y , Mancini , G M S , Sztriha , L , Im , K , Amrom , D , Andermann , E , Paetau , R , Lehesjoki , A-E , Walsh , C A & Lehtinen , M K 2018 , ' Sodium Channel SCN3A (Na(V)1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development ' , Neuron , vol. 99 , no. 5 , pp. 905-+ .

Title: Sodium Channel SCN3A (Na(V)1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development
Author: Smith, Richard S.; Kenny, Connor J.; Ganesh, Vijay; Jang, Ahram; Borges-Monroy, Rebeca; Partlow, Jennifer N.; Hill, R. Sean; Shin, Taehwan; Chen, Allen Y.; Doan, Ryan N.; Anttonen, Anna-Kaisa; Ignatius, Jaakko; Medne, Livija; Bönnemann, Carsten G.; Hecht, Jonathan L.; Salonen, Oili; Barkovich, A. James; Poduri, Annapurna; Wilke, Martina; de Wit, Marie Claire Y.; Mancini, Grazia M. S.; Sztriha, Laszlo; Im, Kiho; Amrom, Dina; Andermann, Eva; Paetau, Ritva; Lehesjoki, Anna-Elina; Walsh, Christopher A.; Lehtinen, Maria K.
Contributor organization: Anna-Elina Lehesjoki / Principal Investigator
Department of Medical and Clinical Genetics
Neuroscience Center
Research Programme for Molecular Neurology
Research Programs Unit
University of Helsinki
Department of Diagnostics and Therapeutics
HUS Medical Imaging Center
Children's Hospital
Lastenneurologian yksikkö
Date: 2018-09-05
Language: eng
Number of pages: 16
Belongs to series: Neuron
ISSN: 0896-6273
Abstract: Channelopathies are disorders caused by abnormal ion channel function in differentiated excitable tissues. We discovered a unique neurodevelopmental channelopathy resulting from pathogenic variants in SCN3A, a gene encoding the voltage-gated sodium channel Na(V)1.3. Pathogenic Na(V)1.3 channels showed altered biophysical properties including increased persistent current. Remarkably, affected individuals showed disrupted folding (polymicrogyria) of the perisylvian cortex of the brain but did not typically exhibit epilepsy; they presented with prominent speech and oral motor dysfunction, implicating SCN3A in prenatal development of human cortical language areas. The development of this disorder parallels SCN3A expression, which we observed to be highest early in fetal cortical development in progenitor cells of the outer subventricular zone and cortical plate neurons and decreased postnatally, when SCN1A (Na(V)1.1) expression increased. Disrupted cerebral cortical folding and neuronal migration were recapitulated in ferrets expressing the mutant channel, underscoring the unexpected role of SCN3A in progenitor cells and migrating neurons.
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: draft

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